The Truth About Off-Label Medications & PCOS

Polycystic ovary syndrome (PCOS) is one of the most common hormonal disorders in the world, affecting about one in 10 women and people with wombs of reproductive age in the UK. It is quite a varied condition and while it’s most commonly characterised by irregular periods, high levels of androgen hormones like testosterone, and follicles or fluid-filled sacs in the ovaries, you need to tick a number of boxes before you can be formally diagnosed.

PCOS can also be associated with elevated levels of oestrogen, luteinising hormone, insulin and anti-Müllerian hormone, as well as many other subtle hormone abnormalities. These can affect ovarian function, menstrual cycle, fertility, hair growth, hair loss, body weight, skin (especially leading to acne) and general health. Some people may have no symptoms; others are severely affected.

It can be linked to other problems, too, such as type 2 diabetes, cardiovascular disease and infertility, and is known to have a knock-on effect on the self-esteem and mental health of the sufferer. As such it is a complex disorder that requires individualised treatment.

The first recommended course, according to Professor Adam Balen, spokesperson for the Royal College of Obstetricians and Gynaecologists (RCOG), is lifestyle-based: eating a varied and healthy diet which contains high levels of nutrients like vitamin D, zinc and magnesium, maintaining a good level of exercise and proper sleep hygiene "is important for general health, and can especially help to manage PCOS", he says.

Medications can also be prescribed to treat one or a few relating symptoms, particularly hyperandrogenism (higher levels of androgen hormones, which can lead to acne, hirsutism, hair loss and irregular periods) and insulin resistance (which can lead to inflammation, weight gain and a greater risk of type 2 diabetes or heart disease). 

The most effective treatment for hyperandrogenism is a combination of oestrogen and an anti-androgen. Professor Balen says: "Any of the combined oral contraceptive pills can help manage symptoms and can also regulate or induce periods [but] specific anti-androgens are found in some types of the combined oral contraceptive pill, including Dianette. Another contraceptive pill called Yasmin also contains a derivative of spironolactone and can be effective for women with PCOS who have acne or unwanted hair growth."

However, this is not the only medication available. If you are unable to take oral contraceptives for whatever reason, there are off-label alternatives.

Spironolactone is a weak diuretic that is used to treat high blood pressure. It works by blocking the effects of androgens such as testosterone, which stimulate the sebaceous glands to produce more sebum (oil) which, combined with the build-up of dead skin cells, can clog pores and lead to acne breakouts. "Spironolactone blocks the action of androgens to help improve hormonal acne," says Dr Zainab Laftah, consultant dermatologist at The Shard. It does this, she explains, "by blocking the two androgen hormones dihydrotestosterone and testosterone from binding. It also increases the clearance of testosterone to reduce circulating levels."

Spironolactone was initially developed to treat heart failure and high blood pressure but its benefits for hormonal acne were discovered in women who had concurrent high blood pressure and PCOS. As such, it is sometimes considered as a treatment option for hormonal acne even though the drug is not licensed for this use. 

Consultant dermatologist Dr Anjali Mahto adds: "Spironolactone should only be prescribed by a consultant dermatologist on the GMC [General Medical Council] specialist register with experience in its use and management of side effects in the context of acne." It is also prescribed by gynaecologists for PCOS.

Side effects can include passing urine frequently, menstrual irregularities, breast tenderness and swelling, nausea and increased potassium levels. Dr Mahto explains: "In patients with a poorly functioning heart or lungs it may have the ability to increase one of the salts in your blood known as your potassium." Additionally, spironolactone can cause irregular bleeding and should not be used by anyone who is considering pregnancy as it can be harmful to the foetus.

"Spironolactone may help with these [hyperandrogenism] symptoms in women for whom the combined oral contraceptive pill is not able to be used – for example those who have a high BMI or with high blood pressure," adds Professor Balen.

Metformin is commonly used for controlling blood glucose and is licensed in the UK for treating type 2 diabetes, particularly in people who are overweight. It reduces glucose production in the liver and improves the insulin sensitivity of other cells. Many women with PCOS have insulin resistance (which can also disturb the normal balance of hormones) and the effects of metformin on the body's response to insulin suggest it might be helpful in managing the symptoms of PCOS for women who don't want to take, or aren’t suitable for, other treatments.

Professor Balen says: "There is a suggestion that metformin can help manage the symptoms of PCOS by lowering the body’s insulin and blood sugar levels. Large studies however have failed to demonstrate any clear benefit from the use of metformin and so we only recommend it for women with a proven problem with high glucose levels or what is known as impaired glucose tolerance, or type 2 diabetes." This is backed up by the summary of evidence published by NICE (National Institute for Health and Care Excellence), entitled: "Polycystic Ovary Syndrome: Metformin in Women Not Planning Pregnancy."

Possible side effects of metformin include nausea, stomach pain, diarrhoea or loss of appetite. Metformin can also stimulate fertility so if it is prescribed to a woman with PCOS who is not trying to get pregnant, suitable contraception should also be used.

Medications go through a long, expensive process to be licensed. The drug company has to prove that the drug works for the illness or condition and that it is safe to use. This is done through clinical trials, which take time and money to be done well. This means that once a drug is on the market, the company may not decide to extend its original licence, even when the drug is found to treat other symptoms.

As things stand, there is no medication licensed to treat PCOS and off-label medicines such as metformin and spironolactone will generally be considered on an individual basis where there is a good clinical reason to prescribe them. The medications need to be monitored to ensure that they are working properly, ideally by an endocrine specialist, qualified dermatologist or gynaecologist. But as Professor Wiebke Arlt, director of the Institute of Metabolism and Systems Research at the University of Birmingham, explains to R29: "Often patients are not referred for further specialist assessment by their GP. Each woman has to be individually assessed for the needs and risk of any medication to improve symptoms."

Because of the complex nature of the condition, Professor Balen adds: "All treatments for women with PCOS should be focused on their individual symptoms and tailored to fit their specific needs, which also may change over time."

There are other factors at play as to why medication is yet to be licensed for PCOS. As Professor Arlt puts it: "PCOS, like other significant women’s health issues, has not been the focus of funding bodies or pharmaceutical funding bodies." This is partly due to sexism and partly due to a misunderstanding about PCOS itself: despite affecting the ovaries and fertility, it is primarily a metabolic – not a gynaecological – disorder. Within this framework there is more scope for research into managing and treating PCOS directly.

In the meantime, if you have PCOS and are struggling to manage your symptoms, the RCOG encourages you to speak to your doctor and ask them to refer you to a gynaecologist (or endocrinologist) specialising in PCOS. A specialist will discuss the options with you and decide what will be the best way of managing your symptoms.